Improved tolerance to sequential glucose loading (Staub-Traugott effect): size and mechanisms

Improved glucose tolerance to sequential glucose loading (Staub-Traugott effect) is an important determinant of day-to-day glycemic exposure. Its mechanisms have not been clearly established. We recruited 17 healthy volunteers to receive two sequential oral glucose tolerance tests (OGTTs), at time 0 min and 180 min (Study I). The protocol was repeated on a separate day (Study II) except that plasma glucose was clamped at 8.3 mmol/l between 60 and 180 min. β-Cell function was analyzed by mathematical modeling of C-peptide concentrations. In a subgroup, glucose kinetics were measured by a triple-tracer technique (infusion of [6,6-2H2]glucose and labeling of the 2 glucose loads with [1-2H]glucose and [U-13C]glucose). In both Studies I and II, the plasma glucose response to the second OGTT equaled 84 ± 2% (P = 0.003) of the response to the first OGTT. Absolute insulin secretion was lower (37.8 ± 4.3 vs. 42.8 ± 5.1 nmol/m2, P = 0.02), but glucose potentiation (i.e., higher secretion at the same glycemia) was s...